CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-001317
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase RNF8 
Protein Synonyms/Alias
 hRNF8; RING finger protein 8 
Gene Name
 RNF8 
Gene Synonyms/Alias
 KIAA0646 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
80QWTIMDNKSLNGVWLubiquitination[1]
192QPVKSQGKGEVASTPubiquitination[1]
214LTALEPSKTTGAPIYubiquitination[1]
235TEVHHEQKASNSSASubiquitination[2]
284TQKGNSKKVVQMEQEubiquitination[1]
334LEIAQGEKDLKQQLAubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 
Functional Description
 E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'- linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin- conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggraving telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2. 
Sequence Annotation
 DOMAIN 38 92 FHA.
 ZN_FING 403 441 RING-type.
 MOD_RES 157 157 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; Cell cycle; Cell division; Chromatin regulator; Chromosome; Complete proteome; DNA damage; DNA repair; Ligase; Metal-binding; Mitosis; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Telomere; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 485 AA 
Protein Sequence
MGEPGFFVTG DRAGGRSWCL RRVGMSAGWL LLEDGCEVTV GRGFGVTYQL VSKICPLMIS 60
RNHCVLKQNP EGQWTIMDNK SLNGVWLNRA RLEPLRVYSI HQGDYIQLGV PLENKENAEY 120
EYEVTEEDWE TIYPCLSPKN DQMIEKNKEL RTKRKFSLDE LAGPGAEGPS NLKSKINKVS 180
CESGQPVKSQ GKGEVASTPS DNLDPKLTAL EPSKTTGAPI YPGFPKVTEV HHEQKASNSS 240
ASQRSLQMFK VTMSRILRLK IQMQEKHEAV MNVKKQTQKG NSKKVVQMEQ ELQDLQSQLC 300
AEQAQQQARV EQLEKTFQEE EQHLQGLEIA QGEKDLKQQL AQALQEHWAL MEELNRSKKD 360
FEAIIQAKNK ELEQTKEEKE KMQAQKEEVL SHMNDVLENE LQCIICSEYF IEAVTLNCAH 420
SFCSYCINEW MKRKIECPIC RKDIKSKTYS LVLDNCINKM VNNLSSEVKE RRIVLIRERK 480
AKRLF 485 
Gene Ontology
 GO:0000781; C:chromosome, telomeric region; ISS:UniProtKB.
 GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0035861; C:site of double-strand break; IDA:UniProtKB.
 GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
 GO:0003682; F:chromatin binding; IDA:UniProtKB.
 GO:0042393; F:histone binding; IDA:UniProtKB.
 GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0051301; P:cell division; IEA:UniProtKB-KW.
 GO:0006303; P:double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
 GO:0043486; P:histone exchange; ISS:UniProtKB.
 GO:0070535; P:histone H2A K63-linked ubiquitination; IDA:UniProtKB.
 GO:0033523; P:histone H2B ubiquitination; ISS:UniProtKB.
 GO:0036297; P:interstrand cross-link repair; TAS:UniProtKB.
 GO:0045190; P:isotype switching; ISS:UniProtKB.
 GO:0007067; P:mitosis; IEA:UniProtKB-KW.
 GO:0045900; P:negative regulation of translational elongation; IMP:UniProtKB.
 GO:0045739; P:positive regulation of DNA repair; IDA:UniProtKB.
 GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
 GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
 GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
 GO:0007286; P:spermatid development; ISS:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB. 
Interpro
 IPR017335; E3_Ub_ligase_RNF8.
 IPR000253; FHA_dom.
 IPR008984; SMAD_FHA_domain.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR017907; Znf_RING_CS. 
Pfam
 PF00498; FHA
 PF13639; zf-RING_2 
SMART
 SM00240; FHA
 SM00184; RING 
PROSITE
 PS50006; FHA_DOMAIN
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 
PRINTS